Using functional magnetic resonance imaging (fMRI), scientists have discovered that cocaine-related images trigger the emotional centers of the brains of patients addicted to drugs, even when the subjects are unaware they’ve seen anything - and the regions of the brain activated by drug images overlapped substantially with those activated by sexual ones.

A team of researchers at the University of Pennsylvania, led by Dr. Anna Rose Childress and Dr. Charles O’Brien, showed cocaine patients photos of drug-related cues like crack pipes and chunks of cocaine. The images flashed by in just 33 milliseconds - so quickly that the patients were not consciously aware of seeing them. Nonetheless, the unseen images stimulated activity in the limbic system, a brain network involved in emotion and reward, which has been implicated in drug-seeking and craving.

“This is the first evidence that cues outside one’s awareness can trigger rapid activation of the circuits driving drug-seeking behavior,” said NIDA director Dr. Nora Volkow. “Patients often can’t pinpoint when or why they start craving drugs. Understanding how the brain initiates that overwhelming desire for drugs is essential to treating addiction.”

Both cocaine (A) and sexual (B) cues produced activation in amygdala and ventral striatum/ventral pallidum/substantia innominata, and insula, as well as the OFC (OFC not shown). Statistical parametric t maps were generated by SPM 2 thresholded for display (color bar: 2 t 5) on the single-subject MNI brain template (“Colin”) in MRICro. Coronal brain sections on the left in (a) and (b) are at y = −6 mm; images on the right in (A) and (B) are at y = 10 mm and y = 6 mm, respectively. The response to “unseen” cocaine cues in a large bilateral ventral pallidum/left amygdala cluster (C) strongly predicted (peak voxel, MNI x, y, z coordinates: −14, −6, −6; t = 7.11; p = 0.000 uncorrected - p = 0.015 cluster-corrected) future affective response to visible cocaine cues (D; r = 0.92). Brain response to 33 msec “unseen” aversive cues (not shown; see Figure S1 in Supporting Materials) varied across individuals, with increased activity in the insula predicting the later affective response to visible aversive cues. Abbreviations: R: right, L: left, v: ventral, amyg: amygdala, si: substantia innominata, tp: temporal pole. NOTE: The ventral boundary of the BOLD acquisition plane for the current studies is z = −40; temporal pole activations may extend ventrally below the acquisition plane.

To verify that the patterns of brain activity triggered by the subconscious cues reflected the patients’ feelings about drugs, Childress and her colleagues gave the patients a different test two days later, allowing them to look longer at the drug images. The patients who demonstrated the strongest brain response to unseen cues in the fMRI experiment also felt the strongest positive association with visible drug cues. Childress notes, “It’s striking that the way people feel about these drug-related images is accurately predicted by how strongly their brains respond within just 33 milliseconds.”

Because Childress and her colleagues also found that the regions of the brain activated by drug images overlapped substantially with those activated by sexual images, it supports the scientific consensus that addictive drugs usurp brain regions that recognize natural rewards needed for survival, like food and sex.

According to Childress, these results could improve drug treatment strategies. “We have a brain hard-wired to appreciate rewards, and cocaine and other drugs of abuse latch onto this system. We are looking at the potential for new medications that reduce the brain’s sensitivity to these conditioned drug cues and would give patients a fighting chance to manage their urges.”

Funded by the National Institute on Drug Abuse (NIDA), part of the National Institutes of Health (NIH).

Citation: Childress AR, Ehrman RN, Wang Z, Li Y, Sciortino N, et al (2008) Prelude to Passion: Limbic Activation by ‘‘Unseen’’ Drug and Sexual Cues. PLoS ONE 3(1): e1506. doi:10.1371/journal.pone.0001506